Iztron 500 mg

Hypersensitivity
As with azithromycin and other macrolides, rare serious allergic reactions, including angioedema and anaphylaxis (rarely fatal), have been reported. Some of these reactions with azithromycin have resulted in recurrent symptoms and required longer period of observation and treatment.

Hepatotoxicity
Since liver is the principal route of elimination for azithromycin, the use of azithromycin should be undertaken with caution in patients with significant hepatic disease.

In patients with mild (class A) to moderate (class B) hepatic impairment, there is no evidence of a marked change in serum pharmacokinetics of azithromycin. In these patients, urinary recovery of azithromycin appears to increase, perhaps to compensate for reduced hepatic clearance. Hence no dose adjustment is recommended for patients with mild to moderate hepatic impairment.

Ergot derivatives
In patients receiving ergot derivatives, ergotism has been precipitated by coadministration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergot and azithromycin. However, because of the theoretical possibility of ergotism, azithromycin and ergot derivatives should not be coadministered.

As with any antibiotic preparation, observation for signs of superinfection with nonsusceptible organisms, including fungi is recommended.

Clostridium difficile-associated diarrhea
Clostridium difficile associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including azithromycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Penicillin is the usual drug of choice in the treatment of Streptococcus pyogenes infections and the prophylaxis of rheumatic fever. Azithromycin is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx. Because some strains are resistant to azithromycin, susceptibility test should be performed when patients are treated with azithromycin. If an allergic reaction occurs, azithromycin should be discontinued and appropriate therapy should be instituted. The physician should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.

Azithromycin should not be used in patients with pneumonia who are judged to be inappropriate for outpatient oral therapy because of moderate to severe illness or risk factors e.g. any of the following:

• patients with nosocomially acquired infections,
• patients with known or suspected bacteremia,
• patients requiring hospitalization,
• elderly or debilitated patients, or
• patients with significant underlying health problems that may compromise their ability to respond to their illness (including immunodeficiency or functional asplenia).

Renal impairment
In patients with severe renal impairment (GFR <10 ml/min), a 33% increase in the systemic exposure to azithromycin was observed. No dose adjustment is needed in patients with mild renal impairment (creatinine clearance >40 ml/minute) but there are no data regarding azithromycin usage in patients with more severe renal impairment; thus, caution should be exercised before prescribing azithromycin in these patients.

Prolongation of the QT interval
Prolonged cardiac repolarization and QT interval, imparting a risk of developing cardiac arrhythmia and torsades de pointes, have been seen in treatment with macrolides, including azithromycin. Therefore, caution is required when treating:

• Patients with congenital or documented QT prolongation.
• Patients currently receiving treatment with other active substances known to prolong QT interval e.g. antiarrhythmics of classes IA and III; antipsychotic agents; antidepressants; and fluoroquinolones.
• Patients with electrolyte disturbance, particularly in cases of hypokalemia and hypomagnesemia.
• Patients with clinically relevant bradycardia, cardiac arrhythmia, or cardiac insufficiency.
• Elderly patients: elderly patients may be more susceptible to drug-associated effects on the QT interval.